Reconstructive bone surgery techniques commonly utilize two sources of material for repairing bone defects caused by congenital anomaly, disease, or trauma. They are autologous bone grafts harvested from the same patients in which they are then implanted, and foreign material (alloplastic) grafts. Both are used to fill voids left by the removed defects, and both have significant problems associated with their use.
Autologous bone grafts are usually harvested from the calvarium, ribs, ilicac crests, and tibia. The harvest time and morbidity associated with such donor sites is often greater than that for the primary reconstruction. In addition, autologous grafts are limited in their size and shape, the quantity of bone obtainable, and often have unpredictable resorption rates.
Alloplastic materials used for bone reconstruction include silicone, methylmethacrylate, ceramic (hydroxyapatite), polytetrafluoroethylene, and titanium. Complications associated with the use of such graft materials include foreign body reactions, extrusion, and infection. The fact that a wide variety of such materials have been used in the past and are used currently indicates that no single material has been found that is superior to the others and that overcomes the aforementioned problems.
In recent years, attention has focused on experimental work in the field of allogenic demineralized bone grafts, that is, demineralized bone graft materials taken from a cadaver of the same species as the patient. Such grafts have shown a unique ability to induce undifferentiated mesenchymal cells to form cells that are part of the endochondral bone formation cascade. The transformed cell types include chondroblasts and osteoblasts and they appear in a characteristic time sequence. Application in several animal models have successfully demonstrated that demineralized bone heals by the mechanism of osteoinduction rather than osteoconduction or "creeping substitution" found in conventional grafts. (Mulliken et al, Induced Osteogenesis--The Biological Principle and Clinical Applications, J. of Surg. Res., Vol. 37, p. 487, 1984). This implies a transformation of an undifferentiated cell into one with a specific function as opposed to the migration of an already differentiated cell type into the area of interest.
Clinically, decalcified autogenous implants have been successfully used on a small scale for spinal fusions and surface-demineralized allogenic cortical bone for intertransverse process fusions. (Urist, Surface Decalcified Allogenic Bone Implants--A Preliminary Report of Ten Cases and Twenty Five Comparable Operations with Undecalcified Lyophilized Bone Implants, Clin. Orthop., Vol. 546, p. 37, 1968; Knapp et al, Use of Cordical Cancellous Allograft for Posterior Spinal Fusion, Clin. Orthop., Vol. 229, p. 98, 1988). It has also been shown that the volume of bone induced by the demineralized grafts is proportional to the external surface area of the implanted matrix. (Glowacki et al, Application of the Biological Principle of Induced Osteogenesis for Craniofacial Defects, Lancet, Vol. 2, p. 959, 1981). This is of importance because it means that it is possible to fill a bony defect of known dimensions with the end result being living integrated bone.
Since demineralization requires intimate exposure of bone matrix to the demineralizing agent (dilute hydrochloric acid), only very small sections of intact cadaver bone have been successfully used for reconstruction. More commonly, the cadaver bone (from an allogenic source, although material from xenogenic sources has been used experimentally) is pulverized into tiny particles of specific size so that bone material may be thoroughly contacted by the demineralizing agent. The treated particles are then washed, heated, and finally combined with water to form a paste that has been referred to as demineralized bone matrix (DBM). Under ideal conditions, when the DBM paste is surgically implanted within the body to repair a bony defect, it transforms mesenchymal stem cells into chondroblasts that form cartilage and, over a period of a few months, evolve into solid bone which is capable of remodelling. Until such transition has occurred, however, the area of restorative treatment provides no appreciable structural strength.
Accordingly, a main aspect of this invention lies in providing a rigid graft material that may be dimensioned to replace a section of a patient's bone and that will retain its structural integrity from the time of implantation and throughout the period of osteoinduction and assimilation. It is also an aspect of this invention to provide a method for treating cadaver bone so that rigid allograft sections of any desired size may be obtained and used for implantation. It is a specific object of the invention to provide a method for demineralizing cadaver bone segments of any required size, including relatively large sections, and of enhancing the osteoinductive potential of such allografts.
Briefly stated, demineralization treatment and osteoinductive potential are enhanced by mechanically texturing the grafts with a reproducible geometric pattern of holes or pores, thereby increasing the surfaces exposed to the demineralizing agent and subsequently exposed for interaction with the mesenchymal cells. The transversely-extending holes should have diameters within the general range of 200 to 2000 um, preferably 500 to 800 um, and the spacing between adjacent holes should fall within the general range of 100 to 1200 um, preferably 300 to 700 um. The depth of the holes may vary, it being unnecessary for all of the holes or pores to pass completely through the bone section. The preferred partial distance is believed to be about 30 to 50% of the bone thickness, the general range being 5 to 90%.
In the method for preparing the bone allograft, a section of mammalian cadaver bone is first treated to remove all soft tissue, including marrow and blood, and is then textured, preferably by laser, to form a multiplicity of holes of selected size, spacing, and depth. The textured bone section is then immersed and demineralized, preferably in a dilute acid bath (e.g., 0.6 M HCl), and is further treated in a defatting solution to remove remaining marrow and intra-matrix cells. Any remaining cell debris and cell surface antigens are removed during that final step and, by the same process, the graft is also sterilized without at the same process, the graft is also sterilized without at the same time destroying its biological (osteoinductive)activity. Such activity is retained because of the biologically-active extracellular matrix proteins that remain bound to the rigid collagen scaffold of the graft. Following the texturing and chemical steps, the grafts may be freeze-dried and stored in sterile bags at conventional room temperature for periods of up to one year and perhaps longer prior to allogenic implantation.
Other features, advantages, and objects of the invention will become apparent from the specification and drawings.